MicroRNAs represent an abundant class of endogenously expressed 18–25 nucleotide non-coding RNA molecules that function to silence gene expression through a process of post-transcriptional modification. They exhibit varied and widespread functions during normal development and tissue homeostasis, and accordingly their dysregulation plays major roles in many cancer types. Gliomas are cancers arising from the central nervous system. The most malignant and common glioma is glioblastoma multiforme (GBM), and even with aggressive treatment (surgical resection, chemotherapy, and radiation), average patient survival remains less than two years. In this review we will summarize the current findings regarding microRNAs in GBM and the biological and clinical implications of this data.
The traditional structure of medical school curriculum in the United States consists of 2 years of pre-clinical study followed by 2 years of clinical rotations. In this essay, I propose that this curricular approach stems from the understanding that medicine is both a science, or a body of knowledge, as well as an art, or a craft that is practiced. I then argue that this distinction between science and art is also relevant to the field of medical ethics, and that this should be reflected in ethics curriculum in medical education. I introduce and argue for virtue ethics as the best opportunity for introducing practical ethical knowledge to medical trainees.
Lower urinary tract symptoms (LUTS) in aging men are commonly attributed to bladder outlet obstruction from benign prostatic hyperplasia (BPH) but BPH/LUTS often reflects a confluence of many factors. We performed a hierarchical cluster analysis using four objective patient characteristics (age, HTN, DM, and BMI), and five pre-operative urodynamic variables (volume at first uninhibited detrusor contraction, number of uninhibited contractions, Bladder Outlet Obstruction Index (BOOI), Bladder Contractility Index (BCI) and Bladder Power at Qmax) to identify meaningful subgroups within a cohort of 94 men undergoing surgery for BPH/LUTS. Two meaningful subgroups (clusters) were identified. Significant differences between the two clusters included Prostate Volume (95 vs 53 cc; p-value = 0.001), BOOI (mean 70 vs 49; p-value = 0.001), BCI (mean 129 vs 83; p-value <0.001), Power (689 vs 236; p-value <0.001), Qmax (8.3 vs 4.9 cc/sec; p-value <0.001) and post-void residual (106 vs 250 cc; p-value = 0.001). One cluster is distinguished by larger prostate volume, greater outlet resistance and better bladder contractility. The other is distinguished by smaller prostate volume, lower outlet resistance and worse bladder contractility. Remarkably, the second cluster exhibited greater impairment of urine flow and bladder emptying. Surgery improved flow and emptying for patients in both clusters. These findings reveal important roles for both outlet obstruction and diminished detrusor function in development of diminished urine flow and impaired bladder emptying in patients with BPH/LUTS.
was purified and subjected to qRT-PCR or RNASeq. Sequence data was pipelined through the Bowtie/TopHat/Cufflinks/CummeRbund (Tuxedo) packages. Pathview v1.10.1 and Cytoscape were used to perform Kegg pathway and network analysis, respectively. Immunoblot analysis was performed using whole protein lysates or concentrated conditioned media.RESULTS: RNASeq analysis showed that prostate fibroblasts treated with CXCL12 up-regulated the transcript levels of genes that encoded members of the Cullin-RING 3 (CRL3) ubiquitin ligase family of proteins. These proteins form COPII vesicles that transport procollagen from the endoplasmic reticulum to the cell membrane and extracellular space. Western blot analysis showed that CXCL12-treated cells upregulated CRL3 proteins and secreted higher levels of procollagen compared to vehicle and TGFb-treated cells. Procollagen secretion was ablated upon treatment with AMD3100, a CXCR4 antagonist, demonstrating that the observed increased collagen secretion was specifically coupled to CXCL12/CXCR4 axis activation.CONCLUSIONS: The results of these studies are consistent with our hypothesis and present a major new discovery: Activation of the CXCL12/CXCR4 axis promotes fibrosis by increasing both the expression and secretion of collagen.
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